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Japanese Encephalitis
Japanese encephalitis (JE) is an infection of the caused by the (JEV). While most infections result in little or no symptoms, occasional . In these cases, symptoms may include headache, vomiting, fever, confusion and s. This occurs about 5 to 15 days after infection. JEV is generally spread by es, specifically those of the type. and wild birds serve as a reservoir for the virus. The disease mostly occurs outside of cities. Diagnosis is based on blood or testing. Prevention is generally with the , which is both safe and effective. Other measures include avoiding mosquito bites. Once infected, there is no specific treatment, with . This is generally carried out in hospital. Permanent problems occur in up to half of people who recover from JE. The disease occurs in and the . About 3 billion people live in areas where the disease occurs. About 68,000 symptomatic cases occur a year, with about 17,000 deaths. Often, cases occur in s. The disease was first described in 1871. Signs and symptoms The Japanese encephalitis virus (JEV) has an of 2 to 26 days. The vast majority of infections are : only 1 in 250 infections develop into encephalitis. Severe rigors may mark the onset of this disease in humans. Fever, headache and are other s of this disease which may last for a period of between 1 and 6 days. Signs which develop during the acute encephalitic stage include neck rigidity, , , convulsions and a raised body temperature between . is usually developed. Mortality of this disease varies but is generally higher in children. Transplacental spread has been noted. Lifelong neurological defects such as deafness, emotional lability and may occur in those who have had involvement. In known cases, some effects also include nausea, headache, fever, and vomiting. Increased activation following Japanese Encephalitis infection has been found to influence the outcome of viral pathogenesis. Microglia are the resident s of the central nervous system (CNS) and have a critical role in host defense against invading microorganisms. Activated microglia secrete cytokines, such as and , which can cause toxic effects in the brain. Additionally, other soluble factors such as , s, , , and nitrogen species are secreted by activated microglia. In a model of JE, it was found that in the and the , the number of activated microglia was more than anywhere else in the brain closely followed by that in the . In the cortex, the number of activated microglia was significantly less when compared with other regions of the . An overall induction of differential expression of and from different brain regions during a progressive Japanese Encephalitis infection was also observed. Although the net effect of the proinflammatory mediators is to kill infectious organisms and infected cells as well as to stimulate the production of molecules that amplify the mounting response to damage, it is also evident that in a nonregenerating organ such as the brain, a dysregulated innate immune response would be deleterious. In JE the tight regulation of microglial activation appears to be disturbed, resulting in an loop of microglial activation that possibly leads to bystander neuronal damage. In animals, key signs include infertility and abortion in pigs, neurological disease in horses and systemic signs including fever, lethargy and anorexia. Cause It is a disease caused by the -borne (JEV). Virology JEV is a virus from the family , part of the Japanese encephalitis serocomplex of 9 genetically and ically related viruses, some which are particularly severe in , and four known to infect humans including . The enveloped virus is closely related to the and the virus. The positive sense single-stranded genome is packaged in the which is formed by the capsid protein. The outer envelope is formed by envelope protein and is the protective antigen. It aids in entry of the virus into the inside of the cell. The genome also encodes several nonstructural proteins (NS1, NS2a, NS2b, NS3, N4a, NS4b, NS5). NS1 is produced as secretory form also. NS3 is a putative , and NS5 is the viral . It has been noted that Japanese encephalitis infects the of the (ER) and rapidly accumulates substantial amounts of viral proteins. Based on the envelope gene, there are five genotypes (I–V). The Muar strain, isolated from a patient in in 1952, is the prototype strain of genotype V. Genotype IV appears to be the ancestral strain, and the virus appears to have evolved in the Indonesian–Malaysian region. The first clinical reports date from 1870, but the virus appears to have evolved in the mid-16th century. Over sixty complete genomes of this virus had been sequenced by 2010. Diagnosis Japanese encephalitis is diagnosed by commercially available tests detecting JE virus-specific IgM antibodies in serum and /or , for example by IgM capture . JE virus IgM antibodies are usually detectable 3 to 8 days after onset of illness and persist for 30 to 90 days, but longer persistence has been documented. Therefore, positive IgM antibodies occasionally may reflect a past infection or vaccination. Serum collected within 10 days of illness onset may not have detectable IgM, and the test should be repeated on a convalescent sample. For patients with JE virus IgM antibodies, confirmatory neutralizing antibody testing should be performed. Confirmatory testing in the US is only available at CDC and a few specialized reference laboratories. In fatal cases, nucleic acid amplification, and virus culture of autopsy tissues can be useful. Viral antigen can be shown in tissues by . Prevention Infection with Japanese encephalitis confers lifelong . There are currently three available: SA14-14-2, IXIARO (IC51, also marketed in Australia and New Zealand as JESPECT) and ChimeriVax-JE (marketed as IMOJEV). All current vaccines are based on the genotype III virus. A -inactivated mouse-brain derived vaccine was first produced in Japan in the 1930s and was validated for use in Taiwan in the 1960s and in Thailand in the 1980s. The widespread use of vaccine and has led to control of the disease in Japan, Korea, Taiwan, and Singapore. The high cost of this vaccine, which is grown in live mice, means that poorer countries have not been able to afford to give it as part of a routine immunization program. The most common adverse effects are redness and pain at the injection site. Uncommonly, an reaction can develop about four days after injection. Vaccines produced from mouse brain have a risk of neurological complications of around 1 per million vaccinations. However where the vaccine is not produced in mouse brains but using there is little adverse effects compared to , the main side effects are headache and . The neutralizing persists in the circulation for at least two to three years, and perhaps longer. The total duration of protection is unknown, but because there is no firm evidence for protection beyond three years, are recommended every three years for people who remain at risk. Furthermore, there is also no data available regarding the interchangeability of other JE vaccines and IXIARO. In September 2012 the Indian firm has launched an derived vaccine based on SA 14-14-2 strain which was developed in a technology transfer agreement with and is a -free vaccine. Treatment There is no specific treatment for Japanese encephalitis and treatment is supportive, with assistance given for , or control as required. Raised may be managed with . There is no from person to person and therefore patients do not need to be isolated. A breakthrough in the field of Japanese encephalitis therapeutics is the identification of receptor involvement in the disease severity. A recent report of an Indian group demonstrates the involvement of and receptor in severe inflammatory response in Japanese Encephalitis infection of the brain. This study provides a hypothesis of and a new lead in development of appropriate therapeutic against Japanese encephalitis. Epidemiology for Japanese encephalitis per 100,000 inhabitants in 2002 }} Japanese encephalitis (JE) is the leading cause of viral encephalitis in , with up to 70,000 cases reported annually. Case-fatality rates range from 0.3% to 60% and depend on the population and age. Rare outbreaks in U.S. territories in the Western Pacific have also occurred. Residents of rural areas in endemic locations are at highest risk; Japanese encephalitis does not usually occur in urban areas. Countries which have had major epidemics in the past, but which have controlled the disease primarily by vaccination, include , , , and . Other countries that still have periodic epidemics include , , , , , and . Japanese encephalitis has been reported in the and two fatal cases were reported in mainland northern in 1998. There were reported cases in , Myanmar in 2013. The spread of the virus in Australia is of particular concern to Australian health officials due to the unplanned introduction of , a potential vector of the virus, from Asia. However, the current presence on mainland Australia is minimal. There had been 116 deaths reported in Odisha's backward of India in 2016. Human, cattle, and horses are dead-end hosts as the disease manifests as fatal encephalitis. Pigs act as an amplifying host and have a very important role in the epidemiology of the disease. Infection in swine is asymptomatic, except in pregnant sows, when abortion and fetal abnormalities are common sequelae. The most important vector is , which feeds on cattle in preference to humans. The natural hosts of the Japanese encephalitis virus are birds, not humans, and many believe the virus will therefore never be completely eliminated. In November 2011, the Japanese encephalitis virus was reported in in . Recently whole genome research of infected with the Japanese Encephalitis virus has shown that neurons play an important role in their own defense against Japanese Encephalitis infection. Although this challenges the long-held belief that neurons are immunologically quiescent, an improved understanding of the proinflammatory effects responsible for immune-mediated control of viral infection and neuronal injury during Japanese Encephalitis infection is an essential step for developing strategies for limiting the severity of CNS disease. A number of drugs have been investigated to either reduce viral replication or provide neuroprotection in cell lines or studies upon mice. None are currently advocated in treating human patients. *The use of , , and with 6 from sp. or nitidum have been shown to be effective in a mouse model of Japanese encephalitis. * has been shown to impart neuroprotection against Japanese Encephalitis infection in an in vitro study. Curcumin possibly acts by decreasing cellular reactive oxygen species level, restoration of cellular , decreasing signaling molecules, and modulating cellular levels of stress-related proteins. It has also been shown that the production of infective viral particles from previously infected cells are reduced, which is achieved by the inhibition of . * in mice resulted in marked decreases in the levels of several markers, viral titer, and the level of proinflammatory mediators and also prevents damage. Evolution The virus appears to have originated from its ancestral virus in the mid-1500s in the Indonesia-Malaysia region and evolved there into five different genotypes and spread across Asia. The mean evolutionary rate has been estimated to be 4.35 (range: 3.4906 to 5.303 ) nucleotide substitutions per site per year. References Category:Third World medical